It has been known that an adsorbent prepared by immobilizing a ligand on a carrier is used to adsorb and remove harmful substances from blood. For such adsorption and removal, there is a method of continuously treating blood by perfusion of it. As the perfusion method, there are a method of separating blood into a hemocyte (hemocyte component) and plasma component and treating only the plasma component by adsorption and removal, and a direct hemoperfusion method for subjecting the whole blood to adsorption and removal treatment without separating the hemocyte and plasma component.
In general in order to enhance an adsorption efficiency, particle sizes of an adsorbent and a carrier therefor may be decreased to increase an effective surface area. This way of thinking can be realized in, for example, a batch treatment and an adsorption treatment of only the plasma component having a low viscosity and containing no hemocyte without so much difficulty as the direct hemoperfusion method.
On the other hand in the direct hemoperfusion method for treating the whole blood, a method of passing the whole blood through a column filled with an adsorbent (also called on-line method) has been adopted generally. Besides that method, there is a method of putting an adsorbent sparsely in a blood bag, mixing the adsorbent with blood to conduct an adsorption treatment, and then filtrating the adsorbent and returning the blood to a patient (bag method). In any of the methods, since the whole blood contacts directly to a foreign material, i.e. the adsorbent, there occur adhesion, breakage and activation of hemocytes, for example, platelets, etc. and activation of a blood coagulating system, and thus the blood tends to coagulate. This phenomenon is greatly affected by material and particle size of a carrier for an adsorbent and appears significantly particularly as the particle size decreases. Therefore though it was known that an adsorption efficiency is increased by using an adsorbent having a smaller particle size, it has been considered that in the direct hemoperfusion method, minimizing the particle size of the adsorbent was difficult from the viewpoint of securing a stable flow of blood. Particularly in case of the on-line method, if adhesion and aggregation of hemocytes occur, a blood passage is not secured and there arises a problem with the flow of blood. From these points of view, at present a carrier for an adsorbent which has an average particle size exceeding about 400 .mu.m is used.
In the bag method, flow of blood does not come into question particularly, and an adsorbent having a smaller particle size as compared with the on-line method can be used. However even in such a case, when the particle size becomes smaller, the above-mentioned adhesion of hemocytes and coagulation of blood are caused. Thus there is a limit in minimizing the particle size.
As mentioned above, an adsorbent used for the direct hemoperfusion for treating the whole blood cannot always be satisfactory merely by making the particle size smaller. It is important that the adhesion of hemocytes, etc. can be inhibited.
An object of the present invention is to minimize the particle size of a carrier used for the direct hemoperfusion with maintaining excellent flow of blood.
The present inventors have made intensive studies with respect to similarity to heparin, toxicity, interaction with a hemocyte and protein, and the like of a sulfated polysaccharide, and as a result, have found that when a carrier is modified with a sulfated polysaccharide or its salt, even if a particle size of the carrier for direct hemoperfusion is further minimized, high passage of hemocytes is exhibited, activation thereof is inhibited and a coagulation time of blood is not shortened, and thus have completed the present invention.